CASP9 phospho T125
Developmental stage
Expressed at low levels in fetal heart, at moderate levels in neonate heart, and at high levels in adult heart.
Function
Involved in the activation cascade of caspases responsible for apoptosis execution. Binding of caspase-9 to Apaf-1 leads to activation of the protease which then cleaves and activates effector caspases caspase-3 (CASP3) or caspase-7 (CASP7). Promotes DNA damage-induced apoptosis in a ABL1/c-Abl-dependent manner. Proteolytically cleaves poly(ADP-ribose) polymerase (PARP). Cleaves BIRC6 following inhibition of BIRC6-caspase binding by DIABLO/SMAC (PubMed:36758105, PubMed:36758106).
Isoform 2
Lacks activity is an dominant-negative inhibitor of caspase-9.
Post-translational modifications
Cleavages at Asp-315 by granzyme B and at Asp-330 by caspase-3 generate the two active subunits. Caspase-8 and -10 can also be involved in these processing events.
Phosphorylated at Thr-125 by MAPK1/ERK2. Phosphorylation at Thr-125 is sufficient to block caspase-9 processing and subsequent caspase-3 activation. Phosphorylation on Tyr-153 by ABL1/c-Abl; occurs in the response of cells to DNA damage.
(Microbial infection) ADP-riboxanation by C.violaceum CopC blocks CASP9 processing, preventing CASP9 activation and ability to mediate intrinsic apoptosis.
Ubiquitinated by BIRC6; this activity is inhibited by DIABLO/SMAC.
Sequence Similarities
Belongs to the peptidase C14A family.
Tissue Specificity
Ubiquitous, with highest expression in the heart, moderate expression in liver, skeletal muscle, and pancreas. Low levels in all other tissues. Within the heart, specifically expressed in myocytes.
Alternative names
MCH6, CASP9, Caspase-9, CASP-9, Apoptotic protease Mch-6, Apoptotic protease-activating factor 3, ICE-like apoptotic protease 6, APAF-3, ICE-LAP6